Respiratory System Anatomy & Physiology PDF

Respiratory system Anatomy & Physiology Aaron Kitcher ANATOMY OF THE THORAX - ANATOMY OF THE AIRWAYS - AIRWAY MUCOSAL LININGS - ALVEOLAR GAS EXCHANGE & GAS TRANSPORT - THE PHYSIOLOGY OF BREATHING - HEMOGLOBIN / HAEMOGLOBIN - BODY ACID-BASE BALANCE - CONTROL OF BREATHING ANATOMY...

Respiratory system Anatomy & Physiology Aaron Kitcher ANATOMY OF THE THORAX - ANATOMY OF THE AIRWAYS - AIRWAY MUCOSAL LININGS - ALVEOLAR GAS EXCHANGE & GAS TRANSPORT - THE PHYSIOLOGY OF BREATHING - HEMOGLOBIN / HAEMOGLOBIN - BODY ACID-BASE BALANCE - CONTROL OF BREATHING ANATOMY OF THE THORAX Thoracic Overview: 3 Parts: 1: Thoracic Cage (skeletal components) 2: Thoracic Wall (muscular components) 3:Thoracic Cavity (internal area Three Internal Compartments: o Central Mediastinum § Containing the Heart/oesophagus/trachea/nerves/vessels o Left Pleural Cavity § Containing the L-Lung o Right Pleural Cavity § Containing the R-Lung General Function A primary requirement for all body cell activities and growth is oxygen, which is needed to obtain energy from food. The fundamental purpose of the respiratory system is to supply oxygen to the individual tissue cells and to remove their gaseous waste product, carbon dioxide. Breathing, or ventilation, refers to the inhalation and exhalation of air. Air is a mixture of oxygen, nitrogen, carbon dioxide and other gases; the pressure of these gases varies depending on the elevation above sea level. The first, external expiration, occurs only in the lungs, where oxygen from the outside air enters the blood and carbon dioxide leaves the blood to be breathed into the outside air. In the second, called internal respiration, gas exchanges occur between the blood and the body cells, with oxygen leaving the blood and entering the cells at the same time that carbon dioxide leaves the cells and enters the blood.  The respiratory system is an intricate arrangement of spaces and passageways that conduct air into the lungs. These spaces include the nasal cavities, the pharynx common to the digestive and respiratory systems; the voice box, or larynx; the windpipe, or trachea; and the lungs, with their conducting tubes and air sacs. The entire system might be thought of as a pathway for air between the atmosphere and the blood. Structure of the Respiratory System Gas exchange in the lungs occurs across an estimated 300 million tiny (0.25 to 0.50 mm in diameter) air sacs known as alveoli. Their enormous number provides a large surface area (60 to 80 square meters, or about 760 square feet) for the diffusion of gases. The diffusion rate is further increased because each alveolus is only one cell layer thick. The total “air-blood barrier” is only two cells across (an alveolar cell and a capillary endothelial cell) or about 2 μm. There are two types of alveolar cells: designated type I alveolar cells and type II alveolar cells. The type I alveolar cells comprise 95% to 97% of the total surface area of the lung; gas exchange with the blood thus occurs primarily through type I alveolar cells.  These cells are accordingly fragile, where the basement membranes of the type I alveolar cells and capillary endothelial cells fuse, the diffusion distance between blood and air can be as little as 0.3 μm (fig), which is about 1/100th the width of a human hair. The type II alveolar cells are the cells that secrete pulmonary surfactant (discussed later) and that reabsorb Na+ and H2O, thereby preventing fluid buildup within the alveoli. To maximize the rate of gas diffusion between the air and blood, the air-blood barrier provided by the alveoli is extremely thin and has a very large surface area. Despite these characteristics, the alveolar wall isn’t fragile but is strong enough to withstand high stress during heavy exercise and high lung inflation. The great tensile strength of the alveolar wall is provided by the fused basement membranes composed of type IV collagen proteins.  Alveoli are polyhedral in shape and are usually clustered, like the units of a honeycomb. Air within one member of a cluster can enter other members through tiny pores. These clusters of alveoli usually occur at the ends of respiratory bronchioles, the very thin air tubes that end blindly in alveolar sacs. Individual alveoli also occur as separate outpouchings along the length of respiratory bronchioles. Although the distance between each respiratory bronchiole and its terminal alveoli is only about 0.5 mm, these units together constitute most of the mass of the lungs. Top photo: A small bronchiole passes between many alveoli. Bottom photo: The alveoli are seen under a higher power, with an arrow indicating an alveolar pore through which air can pass from one alveolus to another.  The air passages of the respiratory system are divided into two functional zones. The respiratory zone is the region where gas exchange occurs, and it therefore includes the respiratory bronchioles (because they contain separate outpouchings of alveoli) and the terminal alveolar sacs. The conducting zone includes all of the anatomical structures through which air passes before reaching the respiratory zone.  Air enters the respiratory bronchioles from terminal bronchioles, which are the narrowest of the airways that do not have alveoli and do not contribute to gas exchange. The terminal bronchioles receive air from larger airways formed from successive branching of the right and left primary bronchi. These two large air passages, in turn, are continuous with the trachea, or windpipe, located in the neck in front of the oesophagus (a muscular tube carrying food to the stomach). The trachea is a sturdy tube supported by rings of cartilage.  Air enters the trachea from the pharynx, the cavity behind the palate that receives the contents of both the oral and nasal passages. For air to enter or leave the trachea and lungs, however, it must pass through a valvelike opening called the glottis between the vocal folds. The ventricular and vocal folds are part of the larynx, or voice box, which guards the entrance to the trachea. The projection at the front of the throat, commonly called the “Adam’s apple,” is formed by the most prominent cartilage of the larynx. CLINICAL APPLICATION Suppose the trachea becomes occluded through inflammation, excessive secretion, trauma, or aspiration of a foreign object. In that case, creating an emergency opening into this tube may be necessary so that ventilation can still occur. A tracheotomy is the procedure of surgically opening the trachea, and a tracheostomy involves the insertion of a tube into the trachea to permit breathing and to keep the passageway open. A competent physician should perform a tracheotomy only because of the great risk of cutting a recurrent laryngeal nerve or the common carotid artery. In summary, the conducting zone of the respiratory system consists of 1. the mouth, 2. nose, 3. pharynx, 4. larynx, 5. trachea, 6. primary bronchi, 7. and all successive branchings of the bronchioles up to and including the terminal bronchioles. In addition to conducting air into the respiratory zone, these structures serve additional functions: warming and humidification of the inspired air and filtration and cleaning. Important point to remember Regardless of the temperature and humidity of the ambient air, when the inspired air reaches the respiratory zone, it is at a temperature of 37° C (body temperature). It is saturated with water vapour as it flows over the warm, wet mucous membranes that line the respiratory airways so that a constant internal body temperature will be maintained. The lung tissue will be protected from desiccation. The mucus secreted by cells of the conducting zone structures traps small particles in the inspired air and performs a filtration function. This mucus is moved along at a rate of 1 to 2 cm per minute by cilia projecting from the tops of epithelial cells that line the conducting zone. About 300 cilia per cell beat in a coordinated fashion to move the mucus toward the pharynx, where it can either be swallowed or expectorated. As a result of this filtration function, particles larger than about 6μm do not normally enter the respiratory zone of the lungs. The cleansing action of cilia and macrophages in the lungs is diminished by cigarette smoke. Thoracic Cavity The diaphragm, a dome-shaped sheet of striated muscle, divides the anterior body cavity into two parts. The area below the diaphragm, the abdominopelvic cavity, contains the liver, pancreas, gastrointestinal tract, spleen, genitourinary tract, and other organs. Above the diaphragm, the thoracic cavity contains the heart, large blood vessels, trachea, oesophagus, and thymus in the central region and is filled elsewhere by the right and left lungs. The structures in the central region—or mediastinum—are enveloped by two layers of wet epithelial membrane collectively called the pleural membranes. The superficial layer, or parietal pleura, lines the inside of the thoracic wall. The deep layer, or visceral pleura, covers the surface of the lungs. The lungs normally fill the thoracic cavity so that the visceral pleura covering each lung is pushed against the parietal pleura lining the thoracic wall. Thus, there is little or no air between the visceral and parietal pleura under normal conditions. There is, however, a “potential space”—called the intrapleural space—that can become a real space if the visceral and parietal pleurae separate when a lung collapses. The normal position of the lungs in the thoracic cavity is shown in the radiographs below. A cross section of the thoracic cavity. In addition to the Radiographic (x-ray) views of the chest. These are x- lungs, the mediastinum and pleural membranes are rays (a) of a normal female and (b) of a normal male. visible. The parietal pleura is shown in green, and the visceral pleura in blue.  PHYSICAL ASPECTS OF VENTILATION Air movement into and out of the lungs occurs due to pressure differences induced by changes in lung volumes. Ventilation is influenced by the physical properties of the lungs, including their compliance, elasticity, and surface tension. Movement of air from higher to lower pressure between the conducting zone and the terminal bronchioles occurs due to the pressure difference between the two ends of the airways. Airflow through bronchioles, like blood flow through blood vessels, is directly proportional to the pressure difference and inversely proportional to the frictional resistance to flow. Changes in lung volumes induce pressure differences in the pulmonary system. The lungs’ compliance, elasticity, and surface tension are physical properties that affect their functioning. Intrapulmonary and Intrapleural Pressures Think of the visceral and parietal pleurae as stuck to each other like two wet pieces of glass. The intrapleural space between them contains only a thin layer of fluid secreted by the parietal pleura. This fluid is like the interstitial fluid in other organs; it is formed as a filtrate from blood capillaries in the parietal pleura and drained into lymphatic capillaries. The major function of the liquid in the intrapleural space is to serve as a lubricant so that the lungs can slide relative to the chest during breathing. Since the lungs normally are stuck to the thoracic wall, for reasons described shortly, they expand and contract with the thoracic wall during breathing. The intrapleural space is thus more a potential space than a real one; it becomes real only if the lungs collapse.  Air enters the lungs during inspiration because the atmospheric pressure is greater than the intrapulmonary, or intra-alveolar, pressure. Because the atmospheric pressure does not usually change, the intrapulmonary pressure must fall below atmospheric pressure to cause inspiration. A pressure below that of the atmosphere is called a subatmospheric pressure or negative pressure. During quiet inspiration, for example, the intrapulmonary pressure may decrease to 3 mmHg below the pressure of the atmosphere. This subatmospheric pressure is shown as − 3 mmHg. Expiration, conversely, occurs when the intrapulmonary pressure is greater than the atmospheric pressure. During quiet expiration, for example, the intrapulmonary pressure may rise to at least +3 mmHg over the atmospheric pressure. Boyle’s Law Changes in intrapulmonary pressure occur as a result of changes in lung volume. This follows from Boyle’s law, which states that the pressure of a given quantity of gas is inversely proportional to its volume. An increased lung volume during inspiration decreases intrapulmonary pressure to subatmospheric levels; air goes in. A decrease in lung volume raises the intrapulmonary pressure above that of the atmosphere, expelling air from the lungs. These changes in lung volume occur as a consequence of changes in thoracic volume, Compliance The lungs are very distensible (stretchable)—they are, in fact, about a hundred times more distensible than a toy balloon. Another term for distensibility is compliance, which here refers to the ease with which the lungs can expand under pressure. Lung compliance can be defined as the change in lung volume per change in transpulmonary pressure. A given transpulmonary pressure, in other words, will cause greater or lesser expansion, depending on the compliance of the lungs. The compliance of the lungs is reduced by factors that produce a resistance to distension, like pulmonary fibrosis. Elasticity The term elasticity refers to the tendency of a structure to return to its initial size after being distended. Because of their high content of elastin proteins, the lungs are very elastic and resist distension. The lungs are normally stuck to the chest wall, so they are always in a state of elastic tension. This tension increases during inspiration when the lungs are stretched and is reduced by elastic recoil during expiration  CLINICAL APPLICATION The elastic nature of lung tissue is revealed when air enters the intrapleural space (as a result of an open chest wound, for example). This condition, pneumothorax, is shown in the figure on the left. As air enters the intrapleural space, the intrapleural pressure rises until it equals the atmospheric pressure. When the intrapleural pressure is the same as the intrapulmonary pressure, the lung can no longer expand. Not only does the lung not expand during inspiration, but it collapses away from the chest wall due to elastic recoil, a condition called atelectasis. Fortunately, a pneumothorax usually causes only one lung to collapse since each lung is in a separate pleural compartment. Surface Tension The forces that act to resist distension include elastic resistance and the surface tension exerted by fluid in the alveoli. The lungs both secrete and absorb fluid to leave only a very thin fluid film on the alveolar surface. The thin film of fluid normally present in the alveolus has a surface tension produced because water molecules at the surface are attracted more to other water molecules than air. As a result, the surface water molecules are pulled tightly together by attractive forces from underneath. This surface tension acts to collapse the alveolus and in the process, increases the pressure of the air within the alveolus. As described by the law of Laplace, the pressure thus created is directly proportional to the surface tension and inversely proportional to the radius of the alveolus. According to this law, the pressure in a smaller alveolus would be greater than in a larger alveolus if the surface tension were the same in both. Surfactant and Respiratory Distress Syndrome The alveolar fluid contains a substance that reduces surface tension. This substance is called surfactant. Surfactant is secreted into the alveoli by type II alveolar cells and consists of phospholipids—primarily phosphatidylcholine and phosphatidylglycerol. Surfactant begins to be produced in late fetal life. For this reason, premature babies are sometimes born with lungs that lack sufficient surfactant and their alveoli are collapsed as a result. This condition is called respiratory distress syndrome (RDS). A full-term pregnancy lasts 37 to 42 weeks. RDS occurs in about 60% of babies born at less than 28 weeks, 30% of babies born at 28 to 34 weeks, and less than 5% of babies born after 34 weeks of gestation. The risk of RDS can be assessed by analysis of amniotic fluid (surrounding the fetus), and mothers can be given exogenous corticosteroids to accelerate the maturation of their fetus’s lungs. Acute respiratory distress syndrome (ARDS). People with septic shock (a fall in blood pressure due to widespread vasodilation due to a systemic infection) may develop a condition called acute respiratory distress syndrome (ARDS). In this condition, inflammation causes increased capillary and alveolar permeability, accumulating a protein-rich fluid in the lungs. This decreases lung compliance and is accompanied by a reduced surfactant, further lowering compliance. As a result, the blood leaving the lungs has an abnormally low oxygen con- centration (hypoxemia).  The thorax must be sufficiently rigid to protect vital organs and provide attachments for a number of short, powerful muscles. However, breathing, or pulmonary ventilation, also requires a flexible thorax that can function as a Between the bony portions of the rib cage are two layers of intercostal muscles: the external intercostal muscles and the internal intercostal muscles. However, there is only one muscle layer between the costal cartilages, and its fibres are oriented similar to those of the internal intercostals. These muscles are, therefore, called the interchondral part of the internal intercostals. Another name for them is the parasternal intercostals. Terms Used to Describe Lung Volumes and Capacities Lung Volumes and Capacities For example, the amount of air expired in each breath is the tidal volume during quiet breathing. The maximum amount of air that can be forcefully exhaled after a maximum inhalation is called the vital capacity, which is equal to the sum of the inspiratory reserve volume, tidal volume, and expiratory reserve volume. The residual volume is the volume of air you cannot expire, even after a maximum forced expiration. This air remains in the lungs because the alveoli and bronchioles normally do not collapse (and the larger airways are noncallable). The expiratory reserve volume is the additional air left in the lungs after an unforced expiration. The sum of the residual volume and expiratory reserve volume is known as the functional residual capacity. During quiet breathing, the tidal volume expiration ends at the functional residual capacity, and the tidal volume inspiration of the next breath begins at that level.  Multiplying the tidal volume at rest by the number of breaths per minute yields a total minute volume of about 6 L per minute. During exercise, the tidal volume and the number of breaths per minute increase to produce a total minute volume as high as 100 to 200 L per minute. Notice that the total minute volume is a useful measurement of breathing because it takes into account both the rate of breathing and the depth of the breaths. Anatomical dead space It should be noted that not all of the inspired volume reaches the alveoli with each breath. As fresh air is inhaled, it is mixed with air in the anatomical dead space. This dead space comprises the conducting zone of the respiratory system—nose, mouth, larynx, trachea, bronchi, and bronchioles—where no gas exchange occurs. Pulmonary Function Tests Pulmonary function may be assessed clinically by means of a technique known as spirometry. In this procedure, a subject breathes in a closed system in which air is trapped within a light plastic bell floating in water. The bell moves up when the subject exhales and down when the subject inhales. The movements of the bell cause corresponding movements of a pen, which traces a record of the breathing called a spirogram  A spirogram showing lung volumes and capacities. A lung capacity is the sum of two or more lung volumes. The vital capacity, for example, is the sum of the tidal volume, the inspiratory reserve volume, and the expiratory reserve volume. Note that residual volume cannot be measured with a spirometer because air cannot be exhaled. Therefore, a spirometer cannot measure the total lung capacity (the sum of the vital capacity and the residual volume).  Spirometry is useful in the diagnosis of lung diseases. On the basis of pulmonary function tests, lung disorders can Restrictive be classified as restrictive or obstructive. In restrictive disorders, such as pulmonary fibrosis, the vital capacity is and reduced to below normal. The rate at which the vital capacity can be forcibly exhaled, however, is normal. In Obstructive disorders that are exclusively obstructive, by contrast, the vital capacity is normal because lung tissue is not damaged. Disorders In asthma, for example, the vital capacity is usually normal but expiration is more difficult and takes a longer time because bronchoconstriction increases the resistance to airflow. Obstructive disorders are, therefore diagnosed by tests that measure the rate of expiration. One such test is the forced expiratory volume (FEV), in which the percentage of the vital capacity that can be exhaled in the first second (FEV1) is measured. An FEV1 that is significantly less than 80% suggests the presence of obstructive pulmonary disease. Pulmonary Disorders People with pulmonary disorders frequently complain of dyspnea, a subjective feeling of “shortness of breath.” However, Dyspnea may occur even when ventilation is normal and may not occur even when the total minute volume is very high, as in exercise. Some of the terms associated with ventilation are defined in the table in the previous slide). Asthma The dyspnea, wheezing, and other asthma symptoms are produced by an airflow obstruction through the bronchioles that occur in episodes, or “attacks.” This obstruction is caused by inflammation, mucous secretion, and bronchoconstriction. Inflammation of the airways is characteristic of asthma and contributes to increased airway responsiveness to agents promoting bronchiolar constriction. Bronchoconstriction further increases airway resistance and makes breathing difficult. Emphysema Alveolar tissue is destroyed in the chronic, progressive condition called emphysema, which results in fewer but larger alveoli. This reduces the surface area for gas exchange. Because alveoli exert a lateral tension on bronchiolar walls to keep them open, the loss of alveoli in emphysema reduces the ability of the bronchioles to remain open during expiration. Collapse of the bronchioles due to the compression of the lungs during expiration produces air trapping, further decreasing the efficiency of gas exchange in the alveoli. The most common cause of emphysema is cigarette smoking. Cigarette smoke directly and indirectly causes Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation with narrowing of the airways and destruction of alveolar walls. The COPD category includes chronic obstructive bronchiolitis, with fibrosis and obstruction of the bronchioles, and emphysema. IMPORTANT DIFFERENCE BETWEEN ASTHMA AND COPD Although asthma is also classified as a chronic inflammatory disorder, it is distinguished from COPD in that the obstruction in asthma is largely reversible with the inhalation of a bronchodilator (Albuterol). Also, asthma (but not COPD) is characterised by airway hyperresponsiveness—an abnormal bronchoconstrictor response to a stimulus. The inflammatory cells characteristic of COPD are macrophages, neutrophils, and cytotoxic T lymphocytes, whereas in asthma, they are helper T lymphocytes, eosinophils, and mast cells. CIGARETTE SMOKE Cigarette smoke contains over 2000 foreign compounds and many free radicals (including reactive oxygen species), which promote inflammation and activate alveolar macrophages and neutrophils. Protein-digesting enzymes released by these activated phagocytes and reactive oxygen species promote the lung damage that results in emphysema. Cigarette smoking also stimulates the proliferation of the mucus-secreting goblet cells of the respiratory tract, and excessive mucus production correlates with the severity of COPD.  In addition, cigarette smoking promotes the remodelling of the small airways, in which additions of fibrous and muscle tissue to the bronchiolar wall narrow the lumen and contribute to the obstruction of airflow. Finally, cigarette smoke promotes remodelling in the lung’s blood vessels, resulting in pulmonary hypertension among COPD patients. It should also be noted that smoking is the major preventable cause of lung cancer, which is responsible for most cancer deaths worldwide. The vast majority of people with COPD are smokers, and cessation of smoking once COPD has begun does not seem to stop its progression. Inhaled corticosteroids, useful in treating asthma inflammation, are of limited value in treating COPD. In addition to the pulmonary problems directly caused by COPD, other pathological changes may occur. These include pneumonia, pulmonary emboli (travelling blood clots), and heart failure. Patients with COPD may develop cor pulmonale—pulmonary hypertension with hypertrophy and eventual right ventricle failure. COPD is currently the fifth leading cause of death worldwide, and it has been estimated that by 2020, it will become the third leading cause of death. GAS EXCHANGE IN THE LUNGS Gas exchange between the alveolar air and the pulmonary capillaries results in an increased oxygen concentration and a decreased carbon dioxide concentration in the blood leaving the lungs. This blood enters the systemic arteries, where blood gas measurements are taken.  Dalton’s law can thus be restated as follows: The total pressure of the gas mixture is equal to the sum of the partial pressures of the constituent gases. Because oxygen constitutes about 21% of the atmosphere, its partial pressure (abbreviated PO2) is 21% of 760 or about 159 mmHg. Nitrogen constitutes about 78% of the atmosphere, so its partial pressure equals 0.78 × 760 = 593 mmHg. These two gases thus contribute about 99% of the total pressure of 760 mmHg: P dry atmosphere = PN2 + PO2 + PCO2 = 760 mmHg Partial Pressures of Gases in Blood The enormous surface area of alveoli and the short diffusion distance between alveolar air and the capillary blood quickly help to bring oxygen and carbon dioxide in the blood and air into equilibrium. This function is further aided by the tremendous number of capillaries that surround each alveolus, forming an almost continuous sheet of blood around the alveoli.  When a liquid and a gas, such as blood and alveolar air, are at equilibrium, the amount of gas dissolved in the fluid reaches a maximum value. According to Henry’s law, this value depends on (1) the solubility of the gas in the fluid, which is a physical constant; (2) the temperature of the fluid— more gas can be dissolved in cold water than in warm water; and (3) the partial pressure of the gas. Because solubility is constant and the blood temperature does not vary significantly, the concentration of a gas dissolved in a fluid (such as plasma) depends directly on its partial pressure in the gas mixture. When water—or plasma—is brought into equilibrium with air at a PO2 of 100 mmHg, the fluid will contain 0.3 ml of O2 per 100 ml fluid at 37° C. If the PO2 of the gas were reduced by half, the amount of dissolved oxygen would also be reduced by half.  At a PO2 of about 100 mmHg, whole blood normally contains almost 20 ml O2 per 100 ml blood; only 0.3 ml of O2 is dissolved in the plasma, and 19.7 ml of O2 is found within the red blood cells. Because only 0.3 ml of O2 affects the PO2 measurement, this measurement would be unchanged if the red blood cells were removed from the sample.  Blood in the systemic veins, delivered to the lungs by the pulmonary arteries, usually has a PO2 of 40 mmHg and a PCO2 of 46 mmHg. After gas exchange in the lungs' alveoli, blood in the pulmonary veins and systemic arteries has a PO2 of about 100 mmHg and a PCO2 of 40 mmHg. The values in arterial blood are relatively constant and clinically significant because they reflect lung function. Blood gas measurements of venous blood are less useful because these values are far more variable. For example, venous PO2 is much lower and PCO2 much higher after exercise than at rest, whereas moderate physical activity does not significantly affect arterial values. Effects of Blood PCO2 and pH on Ventilation Chemoreceptor input to the brain stem modifies the rate and depth of breathing so that, under normal conditions, arterial PCO2, pH, and PO2 remain relatively constant. If hypoventilation (inadequate ventilation) occurs, PCO2 quickly rises and pH falls. The fall in pH occurs because carbon dioxide can combine with water to form carbonic acid, which, as a weak acid, can release H+ into the solution. This is shown in these equations: CO2 + H2O → H2CO3 HCO →H+ +HCO− The oxygen content of the blood decreases much more slowly because of the large “reservoir” of oxygen attached to haemoglobin. Conversely, blood PCO2 quickly falls during hyperventilation, and pH rises because of carbonic acid’s excessive elimination. On the other hand, the oxygen content of blood is not significantly increased by hyperventilation (because the haemoglobin in arterial blood is 97% saturated with oxygen even during normal ventilation). The rate and depth of ventilation are normally adjusted to maintain an arterial PCO2 of 40 mmHg. Hypoventilation causes a rise in PCO2—a condition called hypercapnia. Hyperventilation, conversely, results in hypocapnia. Mechanisms of CO2 Transport - CO2 produced by metabolising cells Produced in Mitochondria - Diffuses into blood. - 3 Routes To The Lungs: o 1. Dissolved In Plasma: § Tissue CO2 → Dissolved Plasma CO2 → Pulmonary Capillaries → Diffusion to Alveoli § 5-10% of Total Body- CO2 o 2. Bound to Hb: § Tissue CO2 → Dissolved RBC CO2 → CO2 + Hb → HbCO2 → Pulmonary Capillaries (PCO2 ↓as dissolved CO2 diffuses to Alveoli) → Dissolved RBC CO2 → Diffusion to Alveoli § 25-30% of Total Body-CO2 § Note: at a different site to O2  3. In Bicarbonate-Ion Form: § Tissue CO2 → Dissolved RBC CO2 → H2CO3 → HCO3 → Exits RBC to Plasma →Pulmonary Capillaries → Re-Enters RBC from Plasma → Dissolved RBC CO2 → Diffusion to Alveoli § 60-70% of Total Body-CO2 § Converted to Bicarb by Carbonic Anhydrase: - Factors Altering CO2 Transport Efficiency: o Bohr Effect: § Not only does ↑ PCO2 cause ↑Carbonic Acid →↓affinity for O2 →Unloading of O2....... o Haldane Effect: § But Unloading of O2 also Favors binding of CO2. § (Deoxy-Hb binds CO2 more readily than Oxy-Hb) CO2 +H2O↔H2CO3 ↔H+ +HCO3 Acid Production: - The Body turns over up to 150Moles of H+ per day – THAT’S A LOT!! - Where does it come from? o Metabolic Processes: § Most H+ comes from Hydrolysing ATP (Ie: Aerobic Metabolism) ATP+H2O→ADP+Pi +H+ Note: The Body turns over ≈40kg of ATP per day! § Much H+ also comes from: Anaerobic Glucose Metabolism Amino Acid Metabolism Fatty Acid B-Oxidation. Nucleic Acid Metabolism. Blood Gas Analysis Normal blood pH: 7.35-7.45 Normal Blood PO2: >80mmHg Normal PCO2: 35-45mmHg Normal Bicarbonate (HCO3): 22-26mmHg Anything below 7.35 is acid and anything above 7.45 is alkaline. The physiological buffering system kicks in when the chemical buffering system fails to keep the pH constant. Maintaining Homeostasis What will happen if PCO2 is increased by more than 45mmHg? Give the interpretation of this arterial blood gas. pH: 7.33. pH:7.37 PCO2: 50 PCO2: 46 HCO3: 30 HCO3: 22 pH: 7.49. pH:7.48 PCO2: 40. PCO2:33 HCO3: 33. HCO3:29